Coronary atherosclerosis is the single most important cause of death and disability in the nation. Whenever the oxygen supplied by the coronary blood flow is inadequate to meet metabolic demands, myocardial ischemia ensues and cardiac function becomes abnormal soon thereafter. The early functional abnormalities of ischemia are reversible, but prolonged ischemia leads to necrosis and permanent loss of myocardial function. Radionuclide angiocardiography is a simple, noninvasive technique which permits measurement of regional left ventricular function in patients with coronary artery disease. Studies using this technique show that almost all patients with coronary artery disease and normal resting left ventricular function develop regional wall motion abnormalities during exercise. A major objective of this grant will be to explore mechanisms by which myocardial ischemia induces functional abnormalities. For this purpose, acute and chronic baboon models of ischemic heart disease will be used to investigate the roles of altered myocardial blood flow, oxygenation, work, and metabolism in producing abnormalities in myocardial function. Acute preparations will allow coronary blood flow and the determinants of cardiac performance to be controlled independently while assessing regional myocardial function and metabolism. Conscious chronically instrumented preparations will be used to investigate the long term effects of ischemia on myocardial function and collateral blood flow in the primate heart. Another part of this study is the evaluation of regional cardiac function in patients at the time of coronary artery bypass grafting. Improvements in technique will make feasible the acquisition of serial scans during operation. These measurements should also be useful for evaluating the effects of anesthesia, operation, and recovery. An increased understanding of mechanisms by which ischemia induces abnormal myocardial function may lead to more effective myocardial preservation with reduction in left ventricular failure, the most common cause of death in coronary disease.